Aromatase expression and outcomes in the P024 neoadjuvant endocrine therapy trial.
BACKGROUND
Expression of aromatase by malignant breast epithelial cells and/or the surrounding stroma implies local estrogen production that could influence the outcome of endocrine therapy for breast cancer.


METHODS
A validated immunohistochemical assay for aromatase was applied to samples from the P024 neoadjuvant endocrine therapy trial that compared tamoxifen and letrozole. The presence of aromatase expression by tumor or stromal cells was correlated with tumor response, treatment induced changes in proliferation index (Ki67), relapse-free survival (RFS) and breast cancer-specific survival (BCSS).


RESULTS
Tumor and stromal aromatase expression were highly correlated (P = 0.0001). Tumor cell aromatase, as a semi-continuous score, also correlated with smaller tumor size at presentation (P = 0.01) higher baseline ER Allred score (P = 0.006) and lower Ki67 levels (P = 0.003). There was no significant relationship with clinical response or treatment-induced changes in Ki67. However, in a Cox multivariable model that incorporated a post-treatment tumor profile (pathological T stage, N stage, Ki67 and ER status of the surgical specimen), the presence of tumor aromatase expression at baseline sample remained a favorable independent prognostic biomarker for both RFS (P = 0.01, HR 2.3, 95% CI 1.2-4.6 for absent expression) and BCSS (P = 0.008, HR 3.76, 95% CI 1.4-10.0).


CONCLUSIONS
Autocrine estrogen synthesis may be most characteristic of smaller, more indolent and ER-rich breast cancers with lower baseline growth rates. However, response to endocrine treatment may not depend on whether the estrogenic stimulus has a local versus systemic source.
Ellis
Matthew J
MJ
Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63119, USA. mellis@dom.wustl.edu
Miller
William R
WR
Tao
Yu
Y
Evans
Dean B
DB
Chaudri Ross
Hilary A
HA
Miki
Yasuhiro
Y
Suzuki
Takashi
T
Sasano
Hironobu
H
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001141:Aromatase / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000187:drug effects / Q000378:metabolism; D000077289:Letrozole; D020360:Neoadjuvant Therapy / Q000379:methods*; D009570:Nitriles / Q000627:therapeutic use; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole; D001141:Aromatase